Approaches to improving the kinetics of adenovirus-delivered genes and gene products

被引:31
作者
Xu, ZL
Mizuguchi, H
Sakurai, F
Koizumi, C
Hosono, T
Kawabata, K
Watanabe, Y
Yamaguchi, T
Hayakawa, T
机构
[1] Natl Inst Hlth Sci, Osaka Branch, Project 3, Osaka 5670085, Japan
[2] Natl Inst Hlth Sci, Div Cellular & Gene Therapy Prod, Tokyo 1588501, Japan
[3] Showa Pharmaceut Univ, Dept Pharmaceut & Biopharmaceut, Tokyo 1948543, Japan
关键词
immunogenic toxicities; biodistribution; cationic liposome; PEGylation; helper-dependent; targeting; in-cis acting element; integration; regulatable expression;
D O I
10.1016/j.addr.2004.12.010
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Adenovirus (Ad) vectors have been expected to play a great role in gene therapy because of their extremely high transduction efficiency and wide tropism. However, due to the intrinsic deficiency of their immunogenic toxicities, Ad vectors are rapidly cleared from the host, transgene expression is transient, and readministration of the same serotype Ad vectors is problematic. As a result, Ad vectors are continually undergoing refinement to realize their potential for gene therapy application. Even after 1999, when a patient fatally succumbed to the toxicity associated with Ad vector administration at a University of Pennsylvania (U.S.) experimental clinic, enthusiasm of gene therapists for Ad vectors has not waned. With great efforts from various research groups, significant advances have been achieved through comprehensive approaches to improving the kinetics of Ad vector-delivered genes and gene products. (c) 2005 Elsevier B.V. All rights reserved.
引用
收藏
页码:781 / 802
页数:22
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